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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sertoli cells play a pivotal role in the regulation of spermatogenesis as they provide the anatomical basis of the blood-testis barrier. In the present paper we report some results of our studies on the ultrastructural features, the responsiveness to FSH, and the ability to secrete androgen-binding protein (ABP) of human Sertoli cells in vitro. The nucleus showed the characteristic foldings of the nuclear membrane, scattered chromatin, and a fibrillar nucleolus. In the cytoplasm Charcot-Boettcher crystals were present and active phagocytic activity was documented by the presence of vacuoles containing lipids and cellular debris. Human Sertoli cells in culture responded to FSH with a maximal rise in cAMP that was approx. 3-fold. This response to FSH is comparable to that reported for the adult rat but lower than that of the immature rat, and suggests that human as well as rat Sertoli cells could have a reduced response to FSH since sexual maturation was achieved. As no evidence has been reported on ABP secretion by human Sertoli cells in culture we evaluated the concentration of this protein in the Sertoli cell spent media. Human Sertoli cells in culture produced ABP and the response to FSH was dose-related. The Kd value of human ABP (hABP) was approx. 7.5 nM, being slightly higher than that of the rat ABP and an order of magnitude different from that of sex hormone-binding globulin (SHBG) present in human plasma. We also measured the association and dissociation rates of dihydrotestosterone-hABP complexes and the Kd/Ka ratio was very close to the value of Kd of the Scatchard analysis. The differences between hABP and SHBG may open the way to the selective measurement of ABP in many conditions of male infertility.
J Steroid Biochem Mol Biol 1992 Oct
PMID:Human Sertoli cells in vitro: morphological features and androgen-binding protein secretion. 132 74

The androgen receptor (AR) is a ligand-dependent DNA transcription factor that binds androgens which cause masculinisation of the developing male fetus. Classical abnormalities of receptor function result in the syndrome of androgen resistance, with resultant failure of normal male differentiation. In more recent years, however, mutations in the AR gene have been described in a number of diverse clinical conditions, from male infertility to prostate and breast cancer through to a form of motor neurone disease (Kennedy's disease). This review discusses the various AR gene mutations found in androgen insensitivity syndrome (AIS) and the other conditions described above, and relates how different mutations, or disruption of different functional domains, contributes to the various phenotypes. Mutations that cause complete AIS usually disrupt the DNA or steroid binding ability of the receptor. In partial AIS, mutations generally decrease receptor affinity for ligand, affect thermostability of the protein, or affect the ability of the receptor to activate transcription of responsive genes. Isolated mutations occur in the steroid binding domain of the receptor in prostate cancer, and many cancers have an identical mutation. Similarly, in the two cases of male breast cancer in which AR gene mutations have been described, the mutations in the DNA binding domain of the receptor are alike. In Kennedy's disease a trinucleotide repeat expansion occurs in exon A of the AR gene, which appears to affect ability of the receptor to bind ligand and activate transcription, although the mechanism of neuronal degeneration remains unknown.
Mol Cell Endocrinol 1995 Aug 11
PMID:Defects of androgen receptor function: from sex reversal to motor neurone disease. 748 16

It has been suggested that congenital bilateral absence of the vas deferens (CBAVD), an important cause of male infertility, is a variant of cystic fibrosis (CF). This study describes a defect in chloride conductance across the nasal epithelium of subjects with CBAVD which is dissimilar to that found in patients with CF. It also demonstrates normal sodium transport across the nasal epithelium in these men, in contrast to patients with CF who exhibit increased sodium absorption. The increased frequency of CFTR mutations in these men implicates the CFTR gene in the pathogenesis of this disorder. Genetic analysis of men with CBAVD who were heterozygous for a known CFTR mutation failed to identify a second mutation within any of the exons or introns of the CFTR gene. These results demonstrate that most men presenting with CBAVD are not compound heterozygotes for mutations within the CFTR gene and can be distinguished from individuals with atypical or asymptomatic CF on the basis of the bioelectric properties of their nasal epithelium. We postulate that mutations in the promoter region or at other regulatory sites of the CFTR gene may be responsible for the CBAVD phenotype in a proportion of cases.
Hum Mol Genet 1993 Oct
PMID:Nasal epithelial ion transport and genetic analysis of infertile men with congenital bilateral absence of the vas deferens. 750 92

Dividing eukaryotic cells expressing the herpes simplex virus type 1 thymidine kinase (TK) gene are sensitive to the cytotoxic effect of nucleoside analogs such as acyclovir or ganciclovir (GCV). Transgenic mice with cell-targeted expression of this conditional toxin have been used to create animals with temporally controlled cell-specific ablation. In these animal models, which allow the study of the physiological importance of a cell type, males are sterile. In this study, we showed that this phenomenon is due to testis-specific high-level expression of short TK transcripts initiated mainly upstream of the second internal ATG of the TK gene. This expression is DNA methylation independent. To obtain a suicide gene that does not cause male infertility, we generated and analyzed the properties of a truncated TK (delta TK) lacking the sequences upstream of the second ATG. We showed that when expressed at sufficient levels, the functional properties of delta TK are similar to those of TK in terms of thymidine or GCV phosphorylation. This translated into a similar GCV-dependent toxicity for delta TK- or TK-expressing cells, both in vitro and in transgenic mice. However, delta TK behaved differently from TK in two ways. First, it did not cause sterility in delta TK transgenic males. Second, low-level delta TK RNA expression did not confer sensitivity to GCV. The uses of delta TK in cell-specific ablation in transgenic mice and in gene therapy are discussed.
Mol Cell Biol 1995 Oct
PMID:A truncated herpes simplex virus thymidine kinase phosphorylates thymidine and nucleoside analogs and does not cause sterility in transgenic mice. 756 81

In human in vitro fertilization (I.V.F.), it was first assumed that all the embryos obtained had the same developmental potential whatever the quality of sperm. However, this has not been confirmed. We have used the coculture technique and determined the blastocyst formation rate in three groups of patients: group 1: patients with normal sperm count (> 20 x 10(6)/ml), motility (> 30%), and morphology (> 50%); group 2: patients treated by I.V.F. with frozen donor sperm; group 3: patients with severely impaired sperm quality (< 3 x 10(6) forward motile and morphologically normal spermatozoa per ml). In group 1, we found a strong correlation between cleavage rate and blastocyst formation rate (P < 0.0001) with a blastocyst formation rate comprised between 40% and 50%. This was not true for the two other groups for which the overall number of blastocysts obtained and the number of patients having at least one blastocyst were severely reduced (P < 0.0001). These data are discussed in terms of DNA quality, timing of formation of the pronuclei, and delays in cell cycles at the time of genomic activation. These observations lead to a new approach to the study of fertilizing ability of poor quality sperm. It may help in the decision as to whether couples treated for male infertility should be excluded from I.V.F. protocols.
Mol Reprod Dev 1994 May
PMID:Evidence for a strong paternal effect on human preimplantation embryo development and blastocyst formation. 804 63

Outer dense fibers (ODFs) are located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail and may help to maintain the passive elastic structures and elastic recoil of the sperm tail. We have identified and describe here a human gene that is homologous to the Mst(3)CGP gene family of Drosophila melanogaster and encodes an ODF protein of 241 amino acids. The transcribed region has a size of approximately 1 kb and contains two exons of 416 bp and 406 bp, respectively, not including the 3' untranslated region. The gene is expressed in testis but not in human spleen, kidney, or brain and resembles in this respect the expression of the Drosophila Mst(3)CGP gene family in the male germline. An antiserum raised against a synthetic peptide derived from the N-terminus of the encoded sequence identified a protein of approximately 32 kDa in an extract of human sperm flagella. By Southern-blot analyses and in situ hybridization, the ODF gene was localized to band q22 of chromosome 8. The isolation of a human gene encoding a sperm tail protein may provide the ability to identify and investigate, on the molecular level, possible reasons for human male infertility that are dependent on flagellar disturbances.
Mol Reprod Dev 1993 Dec
PMID:Sequence, expression, and chromosomal assignment of a human sperm outer dense fiber gene. 830 2

Basic chromosomal proteins were extracted from the sperm of fertile and infertile human males. The relative proportions of protamine 1, 2, and 3 were determined by scanning microdensitometry following electrophoresis of total protamine in polyacrylamide gels. The findings were as follows: (1) The proportion of protamine P(2 + 3) in sperm obtained from infertile males was lower than that in fertile males. (2) Protamine P(2 + 3) in infertile human males showed reduced affinity to DNA. The possibility that some cases of human male infertility may be due to mutation within the protamine P2 gene is discussed.
Mol Reprod Dev 1993 Jan
PMID:Human male infertility may be due to a decrease of the protamine P2 content in sperm chromatin. 841 17

In order to minimize the percentage of false-negative results in the zona-free sperm penetration assay (SPA), a wide range of substances and/or physical agents capable of inducing the acrosome reaction (AR) have been incorporated in the incubation medium. These agents can also be used for treatment of severe male infertility using the technique of sperm microinjection under the zona pellucida (SMUZ). In the present review, the percentages of acrosome-reacted spermatozoa induced by several physiological, biochemical or physical agents published in the literature are compared in order to find the most efficient method(s) of inducing the AR in human sperm as a previous requirement of optimizing the technique of SMUZ. A working estimate of the level of efficiency of a given AR inducer is calculated by adding up its range score in each of three different arrangements from the highest to the lowest value of percentages of AR and differences in percentages of AR and penetration indexes between treated and control groups in SPA. The agents able to induce the AR by nonphysiological (electropermeabilization, lysophosphatidyl choline, and freezing-thawing) have better positions in this hierarchical system than those ones which require the active participation of sperm membrane receptors or second messenger systems (progesterone, zona pellucida, and stimulators of protein kinase A). Electropermeabilization appears to be the most efficient AR inducer. However, more possibilities need to be explored to enhance the relatively low percentages of acrosome-reacted spermatozoa shown by infertile men.
Mol Reprod Dev 1993 May
PMID:Zona-free sperm penetration assay and inducers of the acrosome reaction: a model for sperm microinjection under the zona pellucida. 850 86

The tissue expression patterns of 10 mouse testis cDNAs were analysed by RT-PCR to search for new mammalian meiotic genes. The homologue of the rat synaptonemal complex protein gene SCP1 is expressed in embryonic ovary, adult brain and testis. One novel gene is stringently testis specific and another is expressed exclusively in testis and embryonic ovary. The latter clone is not expressed in the testes of adult sex-reversed mice which lack germ cells, and therefore represents a meiosis-specific gene. It is part of a mouse multigene family, members of which are clustered and map genetically and physically to a single region of the X chromosome. We have named this family Ott (ovary testis transcribed). Steady-state levels of a 2.3 kb polyadenylated Ott mRNA are high throughout meiotic prophase in the testis when the X chromosome is generally transcriptionally inactive. A second transcript of 1 kb is also detectable from 4 weeks of age onwards. The two mRNAs have different 3' ends and contain different protein coding information. At least seven Ott genes are transcribed specifically during meiosis and are predicted to encode "pioneer' proteins with an unusual structure, containing tandem arrays of a degenerate eight amino acid repeat. This work could lead to the identification of a human Ott homologue, which is likely to be X-linked and would provide a candidate locus for some cases of male infertility.
Hum Mol Genet 1996 Aug
PMID:Ott, a mouse X-linked multigene family expressed specifically during meiosis. 884 33

The DAZ (Deleted in AZoospermia) and DAZLA (DAZ-like autosomal) genes may be determinants of male infertility. The DAZ gene on the long arm of the human Y chromosome is a strong candidate for the 'azoospermia factor' (AZF). Its role in spermatogenesis is supported by its exclusive expression in testis, its deletion in a high percentage of males with azoospermia or severe oligospermia, and its homology with a Drosophila male infertility gene boule. No DAZ homologous sequences have been found on the mouse Y chromosome. Instead, a Dazla gene was isolated from mouse chromosome 17 and has been considered to be a murine homologue of DAZ. However, the homology between human DAZ and mouse Dazla is not strong, and Dazla contains only one of the seven DAZ repeats found in DAZ. We report the isolation of the human DAZLA gene by screening a human testis cDNA library with a DAZ cDNA clone. DAZLA encodes only one DAZ repeat and shares high homology with the mouse Dazla, indicating that these two genes are homologues. Using a panel of rodent-human somatic cell lines and fluorescence in situ hybridization, the DAZLA gene was mapped to 3p24, a region not known to share homology with mouse chromosome 17. The DAZLA gene may be involved in some familial cases of autosomal recessive male infertility.
Hum Mol Genet 1996 Dec
PMID:The human autosomal gene DAZLA: testis specificity and a candidate for male infertility. 896 56


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